A major issue in human prion diseases is their rapid onset, with few warning signs. Particularly in the case of sporadic Creutzfeldt-Jakob Disease (sCJD), there are not consistent biomarkers or signs of disease until clinical symptoms begin. This makes development of therapeutics for sCJD and other human prion diseases incredibly difficult. Once neurodegeneration begins in the brain, it is hard to stop it or reverse it. This research focuses on developing a better understanding of what is happening on a cellular level in the brain during sCJD using cerebral organoids as a model. Cerebral organoids are, in essence, mini brains. These cerebral organoids, which have functional neurons and other types of brain cells, can be developed by reprogramming human skin cells. In collaboration with researchers at Case Western Reserve, our lab has been given cells from donors with genetic and sporadic prion diseases, as well as from healthy donors. We have successfully used skin cells from donors with genetic prion disease to develop cerebral organoids and have seen many changes in these organoids compared to those derived from healthy donors. The focus of this research is to develop cerebral organoids from skin cells from donors with sCJD. Once we develop these organoids, we can look for changes in the health and function of neurons and other cell types in the organoids with sCJD compared to healthy organoids. This can give us more insight into biomarkers and signs of disease that may occur prior to neurodegeneration and symptoms. We also can look for abnormal prion protein in the sCJD organoids, and test different therapeutics to try to reduce these abnormal prion proteins and alleviate neuronal dysfunction. We anticipate that sCJD organoids will most accurately model what is occurring in the brains of patients with sCJD and will be beneficial to uncovering biomarkers of disease and testing therapeutics.